Uptake, toxicity and radiation effects of the boron compounds DAAC-1 and DAC-1 in cultured human glioma cells.
OBJECTIVE
To study the uptake, toxicity and radiation effects in vitro of a diol-amino acid-carborane (DAAC-1) and make comparisons with the previously studied diol-amine-carborane (DAC-1).


METHODS
Toxicity and radiation effects were studied with clonogenic survival, uptake by measuring the cellular boron content and the subcellular distribution was investigated after organelle separation with centrifugation. The studied cell line was human glioma U343.


RESULTS
DAAC-1 showed an accumulation of 1-1.5 times, compared with the culture medium, and was non-toxic up to 47 microg boron/ml. The accumulation of DAC-1 was about 90 times, but toxic effects were detectable already at the concentration 5 microg boron/ml. None of the compounds was localized in the cell nucleus. Following irradiation with thermal neutrons, DAC-1 was about 2.5 times more effective than DAAC-1 and about 4.9 times more effective than neutrons alone, at the survival level 0.2. The dose modifying factors, when compared with the neutron beam alone, were for both DAAC-1 and DAC-1 about 1.5 and about 5 when compared with 60Co-gamma-radiation.


CONCLUSIONS
DAAC-1 was less toxic than DAC-1 but gave less accumulation of boron. Both substances gave significant boron-dependent cell inactivation when the test cells were exposed to thermal neutrons.
Olsson
P
P
Department of Diagnostic Radiology, Uppsala University, Sweden.
Black
M
M
Capala
J
J
Coderre
J
J
Hartman
T
T
Makar
M
M
Malmquist
J
J
Pettersson
J
J
Tilly
N
N
Sjöberg
S
S
Carlsson
J
J
D001880:Boranes / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D016754:Boron Neutron Capture Therapy; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured
D001880:Boranes; C087322:DAC 1